# GHK-Cu (Copper Tripeptide-1)

> GHK-Cu is the copper(II) complex of glycyl-L-histidyl-L-lysine (GHK), a tripeptide that occurs naturally in human plasma, saliva and urine. Also called copper tripeptide-1 or prezatide copper, it is used as a cosmetic ingredient and studied in cell and animal models of wound repair, inflammation, oxidative stress and tissue remodeling. It is not an FDA-approved drug.

Canonical: https://peptideproperties.com/compounds/ghk-cu/

## Identity

- **Class:** Copper & Cosmetic Peptides
- **Also known as:** Copper Tripeptide-1, Copper peptide, Prezatide copper
- **Molecular formula:** C14H23CuN6O4+
- **Molecular weight:** 402.92 g/mol
- **Monoisotopic mass:** 402.1077 Da
- **CAS number:** 89030-95-5
- **PubChem CID:** 71587328
- **InChIKey:** NZWIFMYRRCMYMN-ACMTZBLWSA-M
- **Sequence:** GHK
- **Sequence notes:** Copper(II) complex; free N-terminal amine and free C-terminal carboxylate (no amidation). Copper coordinated by the glycine amine, glycyl-histidine amide nitrogen and histidine imidazole.

## Key facts

- Class: copper-binding tripeptide; cosmetic peptide (INCI: copper tripeptide-1)
- Sequence: three residues, glycine-histidine-lysine (GHK), complexed with one copper(II) ion
- Origin: GHK occurs naturally in human plasma, saliva and urine, and declines with age
- Formula C14H23CuN6O4+; molecular weight 402.92 g/mol (PubChem CID 71587328)
- CAS 89030-95-5; nonproprietary name prezatide copper
- Evidence base: in-vitro and animal studies; no controlled clinical trials for systemic or musculoskeletal use
- Regulatory status: not FDA approved as a drug; used as a cosmetic ingredient

## What Is GHK-Cu?

GHK-Cu is the copper(II) complex of GHK (glycyl-L-histidyl-L-lysine), a tripeptide that occurs naturally in human plasma, saliva and urine. It is also known by the INCI name copper tripeptide-1 and the nonproprietary name prezatide copper.[1]The free peptide GHK has a very high affinity for copper and readily forms the GHK-Cu chelate. Both the peptide and its copper complex have been described as having anti-inflammatory and tissue-remodeling properties in laboratory studies.[2] Reviews generally treat GHK and GHK-Cu together, and several authors propose that GHK acts in the body primarily as a complex with copper 2+.[1]Endogenous GHK declines with age. One report gives average serum levels of about 200 ng/mL at age 20 falling to about 80 ng/mL by age 60.[2] In a small clinical comparison, plasma GHK measured by reversed-phase HPLC was lower in patients with chronic obstructive pulmonary disease (COPD) than in age-matched healthy subjects.[3]GHK-Cu is widely used as an ingredient in anti-wrinkle, dermatological and hair care formulations.[4][5] Outside cosmetics, it is studied as a research compound in models of wound repair, lung injury, muscle wasting and inflammation.

## Chemical Structure and Molecular Identity

GHK-Cu consists of three standard L-amino acids, glycine, histidine and lysine, bound to a single copper(II) ion. PubChem (CID 71587328) lists the complex with the molecular formula C14H23CuN6O4+ and a molecular weight of 402.92 g/mol.The peptide backbone has a free N-terminal amine on glycine and a free C-terminal carboxylate on lysine, with no amidation or acylation. Copper is coordinated by nitrogen atoms from the glycine amine, the glycyl-histidine peptide bond and the histidine imidazole ring, as reflected in the systematic name copper, (glycyl-κN-L-histidyl-κN,κN3-L-lysinato(2-))-.
### Key identifiers

- CAS number: 89030-95-5
- InChIKey: NZWIFMYRRCMYMN-ACMTZBLWSA-M
- UNII: 6BJQ43T1I9
- Synonyms: prezatide copper, copper tripeptide-1, GHK copper, copper peptideGHK-Cu is fairly hydrophilic, with high aqueous solubility and a low partition coefficient. Reviewers note that this limits its passage through the lipophilic stratum corneum and creates formulation challenges, including peptide instability.[6][4] Related derivatives include Pal-GHK, a palmitoylated form of GHK designed to increase lipophilicity.[4]

## Research History and Development

The GHK-Cu literature centers on wound healing and skin biology, with more recent preclinical work in lung disease, skeletal muscle and aging. Much of the foundational literature has been summarized in reviews by Pickart and colleagues.[1][7]Wound repair is a central theme. According to a 2015 review, GHK accelerated healing of skin, hair follicles, gastrointestinal tract, bone tissue and the foot pads of dogs, and induced systemic wound healing in rats, mice and pigs.[1] The review also summarizes reports from cosmetic products of improved skin elasticity, density and firmness and reduced fine lines, although these were not drawn from controlled drug trials.[1]Later research turned to gene-expression data. A 2018 review argued that broad changes in gene expression could explain how one small molecule shows such varied protective and repair activity across tissues.[7] Since 2022, researchers have tested GHK-Cu in mouse models of cigarette smoke exposure, silicosis and smoking-related muscle dysfunction.[8][3][9]No controlled clinical trials of GHK-Cu are described in the reviewed literature. Recent orthopedic and sports medicine reviews group it with other unapproved peptides marketed directly to patients and stress the lack of clinical trials.[10][11][12]

## Mechanisms Studied in Research

Research attributes GHK-Cu's effects to extracellular matrix remodeling, antioxidant and anti-inflammatory signaling, and broad changes in gene expression. Most mechanistic data come from cell culture and animal models.
### Extracellular matrix and tissue remodeling
GHK stimulates both synthesis and breakdown of collagen and glycosaminoglycans and modulates metalloproteinases and their inhibitors. Reported targets include collagen, dermatan sulfate, chondroitin sulfate and the small proteoglycan decorin. The molecule also attracts immune and endothelial cells to sites of injury.[1] Reviews further describe increased elastin synthesis, support of dermal fibroblast function, and blood vessel and nerve outgrowth.[7] An orthopedic review places GHK-Cu among wound-healing peptides that act through angiogenesis, integrin-mediated matrix remodeling and fibroblast activation.[10]
### Oxidative stress and inflammation

- NF-κB and Nrf2: in cigarette-smoke-exposed mice, GHK-Cu reduced NF-κB expression and raised Nrf2 levels in lung tissue.[8]
- SIRT1: in muscle cells and mice, GHK-Cu bound and activated SIRT1, which inhibited FoxO3a activity, deacetylated Nrf2 and increased PGC-1α expression.[3]
- Peroxiredoxin 6: in a silicosis model, GHK-Cu bound PRDX6 and reduced oxidative stress in alveolar macrophages.[9]
- JAK1: in zebrafish larvae, pathway analysis showed downregulation of JAK1 signaling.[5]
### Gene expression
Pickart and colleagues report that GHK can up- or downregulate at least 4,000 human genes, based on gene-expression data.[1] They link this to reported effects on the proteasome system, DNA repair and suppression of NF-κB.[7] These are interpretations of expression data, not demonstrated clinical effects.

## Key Findings From Published Studies

Published findings on GHK-Cu come mainly from cell culture and rodent or zebrafish models, with no controlled clinical trials for musculoskeletal or systemic conditions. The studies below are grouped by evidence type.
### Animal studies

- Ligament graft healing: in a rat model of anterior cruciate ligament reconstruction (72 rats randomized to saline or two GHK-Cu concentrations), intra-articular GHK-Cu reduced side-to-side knee laxity and, in the lower-concentration group, increased graft stiffness at 6 weeks. No differences remained at 12 weeks, and ultimate load, gait and histology did not differ.[13]
- Emphysema: in mice exposed to cigarette smoke for 12 weeks, GHK-Cu attenuated emphysematous changes, partially reversed the MMP-9/TIMP-1 imbalance, lowered IL-1β and TNF-α, and restored glutathione and total antioxidant capacity.[8]
- Silicosis: in a crystalline-silica mouse model, GHK-Cu attenuated lung inflammation and fibrosis without significant systemic toxicity.[9]
- Muscle dysfunction: in cigarette-smoke-exposed mice, GHK-Cu reduced muscle mass loss, increased muscle cross-sectional area and improved grip strength through a SIRT1-dependent pathway.[3]
- Acute inflammation: in zebrafish larvae challenged with copper sulfate or lipopolysaccharide, GHK-Cu reduced neutrophil and macrophage migration, lowered tnf-a, il-1β and il6, raised il-10, and reduced nitric oxide and reactive oxygen species.[5]
- Learning in aging mice: the copper-free peptide GHK prevented acute learning impairment in sleep-deprived aging mice and blocked increases in hippocampal MCP-1 and nitrotyrosine.[14]
### In-vitro studies
GHK-Cu reduced oxidative stress in human alveolar epithelial A549 cells exposed to cigarette smoke extract.[8] In C2C12 myotubes it increased myosin heavy chain, reduced MuRF1 and atrogin-1, and raised mitochondrial content.[3] Cellular studies support GHK as an anti-wrinkle ingredient, and GHK has been reported to restore replicative vitality to fibroblasts after radiation.[4][1]
### Human evidence
Human data are limited. Reviews of topical use describe a surprising absence of clinical studies of GHK-Cu and Pal-GHK in anti-wrinkle products, and note that transport of liposome-encapsulated GHK-Cu through skin has received little study.[4][6] Orthopedic reviewers conclude that no clinical data support GHK-Cu for musculoskeletal conditions and that rigorous human safety data for unapproved peptides are scarce.[11][12]Because published results depend on a correctly formed copper complex, researchers typically verify GHK-Cu identity and purity with HPLC and mass spectrometry certificates of analysis.Because published results depend on a correctly formed copper complex, researchers typically verify GHK-Cu identity and purity with HPLC and mass spectrometry certificates of analysis.

## Regulatory and Research Status

GHK-Cu is not an FDA-approved drug; it is a cosmetic ingredient under the INCI name copper tripeptide-1 and a research compound. A 2026 sports medicine review lists GHK-Cu among unapproved peptides sold directly to patients, largely outside regulatory oversight.[12]Reviewers emphasize that indications, safety and efficacy in humans have not been established through controlled trials.[11] Its broad use in topical cosmetic products contrasts with the limited published data on skin permeability and clinical effectiveness.[4]Current research directions include delivery methods for topical formulations, such as liposomes, cell-penetrating peptides and microneedle pretreatment, along with further preclinical work in lung, muscle and aging models.[6][4][2]

## FAQ

**Is GHK-Cu the same as GHK?**
No. GHK is the free tripeptide glycyl-L-histidyl-L-lysine, while GHK-Cu is GHK bound to a copper(II) ion. GHK has a very high affinity for copper and readily forms this chelate, and reviews often discuss the two together. Some studies use the copper-free peptide, such as work on learning in sleep-deprived aging mice, so the form tested matters when reading results.

**What is the molecular weight of GHK-Cu?**
PubChem lists GHK-Cu (CID 71587328) with a molecular weight of 402.92 g/mol and the molecular formula C14H23CuN6O4+. Its CAS number is 89030-95-5 and its InChIKey is NZWIFMYRRCMYMN-ACMTZBLWSA-M. Commercial material may be supplied as a salt, such as an acetate or TFA salt, which changes the weight of the bulk solid.

**Is GHK-Cu FDA approved?**
No. GHK-Cu is not an FDA-approved drug. It is used as a cosmetic ingredient under the INCI name copper tripeptide-1, and recent sports medicine reviews classify it among unapproved peptides marketed directly to patients. Reviewers note that controlled clinical trials establishing safety and efficacy for any medical use have not been published.

**What is copper tripeptide-1?**
Copper tripeptide-1 is the INCI cosmetic ingredient name for GHK-Cu, the copper(II) complex of glycyl-L-histidyl-L-lysine. The same compound is also listed as prezatide copper, GHK copper and copper peptide. It appears widely in anti-wrinkle, skin care and hair care formulations.

**What does the research on GHK-Cu show?**
Most GHK-Cu research comes from cell culture and animal models. In mice, it attenuated cigarette-smoke-induced emphysema, silica-induced lung fibrosis and smoking-related muscle loss. In a rat ACL reconstruction model, it improved graft healing at 6 weeks but not at 12 weeks. Reviewers note there are no controlled clinical trials supporting medical or musculoskeletal use.

**How is GHK-Cu different from Pal-GHK?**
GHK-Cu is GHK complexed with copper, while Pal-GHK (palmitoyl tripeptide-1) is GHK modified with a palmitoyl fatty-acid chain. Both changes are reported to increase skin permeability compared with the free peptide. Reviewers note that despite wide use of both in anti-wrinkle products, clinical studies of either are largely absent.

**Does GHK-Cu penetrate the skin?**
GHK-Cu is fairly hydrophilic, which limits its passage through the lipophilic outer skin layer. Reviews describe it as relatively skin permeable compared with free GHK and discuss methods studied to improve delivery, including liposomes, cell-penetrating peptides and microneedle pretreatment. Transport of liposome-encapsulated GHK-Cu has received little direct study.

## References

1. Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. BioMed research international 2015. PMID: 26236730
2. Dou Y, Lee A, Zhu L, et al. The potential of GHK as an anti-aging peptide. Aging pathobiology and therapeutics 2020. PMID: 35083444
3. Deng M, Zhang Q, Yan L, et al. Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway. Journal of cachexia, sarcopenia and muscle 2023. PMID: 36905132
4. Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR. Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective. BioImpacts : BI 2025. PMID: 39963574
5. Hu J, Zhang C, Wang F. Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model. European journal of pharmacology 2026. PMID: 41997403
6. Ogórek K, Nowak K, Wadych E, et al. Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes? Molecules (Basel, Switzerland) 2025. PMID: 39795193
7. Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. International journal of molecular sciences 2018. PMID: 29986520
8. Zhang Q, Yan L, Lu J, et al. Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway. Frontiers in molecular biosciences 2022. PMID: 35936787
9. Bian Y, Deng M, Liu J, et al. The glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6. Redox biology 2024. PMID: 38879894
10. Rahman OF, Lee SJ, Seeds WA. Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews 2026. PMID: 41490200
11. Mayfield CK, Bolia IK, Feingold CL, et al. Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians. The American journal of sports medicine 2026. PMID: 41476424
12. Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Sports medicine (Auckland, N.Z.) 2026. PMID: 41966639
13. Fu SC, Cheuk YC, Chiu WY, et al. Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2015. PMID: 25731775
14. Rosenfeld M, Nickel K, Ladiges W. GHK peptide prevents sleep-deprived learning impairment in aging mice. Aging pathobiology and therapeutics 2023. PMID: 37035833